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ADJUSTED SERUM CALCIUM FAILS TO PREDICT IONISED CALCIUM ANY BETTER
THAN TOTAL CALCIUM IN PATIENTS UNDERGOING HAEMODIALYSIS: A NEW
MODEL BASED ON TOTAL CALCIUM, ALBUMIN AND PHOSPHATE BETTER
ESTIMATES IONISED CALCIUM
Wheatley-Baldacchino, M1, Everitt, A1, Barton, I2
Departments of Chemical Pathology1 and Renal Medicine2, Basildon University Hospital
INTRODUCTION: Calcium is present in three fractions in serum - ionised (the biologically active
form), bound to proteins and bound to anions. Current practice in UK laboratories is to adjust calcium
to “correct” for the fraction bound to albumin, using a formula, such as the one we use (Caadjusted =
Catotal + (43 – albumin) x 0.0175), which was derived locally from a patient population with normal
or only mildly impaired renal function . No adjustment is made for the fraction bound to anions such
as phosphate and bicarbonate, the concentrations of which are often abnormal in patients with chronic
kidney disease (CKD). A further complicating factor is that different methods for total calcium and
albumin are in use on different analytical platforms in different laboratories and these methods may
give discrepant results in samples from patients undergoing haemodialysis.
Ionised calcium can now be measured using commercially available analysers. The aim of this study
was to investigate in patients undergoing haemodialysis (i) whether total calcium reflects ionised
calcium, (ii) whether adjusted calcium reflects ionised calcium, (iii) whether it is possible to derive a
model using routine pre-dialysis analytes which better estimates ionised calcium and (iv) if a new
model could be derived, to test it on blood taken post dialysis.
METHODS: Blood was taken from 50 patients before and after haemodialysis and analysed for total
calcium, total protein, albumin, phosphate, bicarbonate and PTH (pre-dialysis only) using standard
laboratory methods. Ionised calcium and pH were measured in blood samples taken into blood gas
syringes using a NOVA pHOx analyser.
RESULTS: In pre-dialysis samples, adjusted calcium (r = 0.62) correlated with ionised calcium no
better than total calcium (r = 0.63). Single-predictor linear regression analysis of the pre-dialysis
samples showed that total calcium, albumin and phosphate were the three analytes which best
correlated with ionised calcium, and the following model was derived which showed a strong
correlation with ionised calcium: Caestimated = 0.48 + 0.398 × Catotal - 0.003 × albumin - 0.02 ×
phosphate. When tested on the post dialysis samples, the estimated calcium derived using this model
correlated well with ionised calcium (r = 0.85) and the model performed better than total calcium (r =
0.81) or adjusted calcium (r = 0.79).
CONCLUSION: If the aim of adjusting serum calcium is to better predict the biologically active
fraction, the currently widely used formula fails to do so, at least in the group of patients with CKD5
whom we studied. This is probably, in part, because a significant amount of calcium is bound to
phosphate, the concentration of which is often abnormal in patients with CKD5. It would be
preferable to measure ionised calcium routinely, but cost and inconvenience may make this
impractical. If the model that we have derived performs well in other groups of patients, consideration
should be given to substituting it for the formula currently used to adjust serum calcium.
The findings of this study have significant implications not just for clinical practice and our standards,
but for all research where serum calcium is either thought to potentially affect the outcome being
measured or is one of the outcomes being measured.